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Biomedical subjects

M Samama

Publications and source records attributed to M Samama.

At least 37 records · Page 2Linked to original sources
PubMed1996

The antithrombotic potential of dalteparin in man assessed indirectly by Wessler's technique.

The aim of this study was to demonstrate the effectiveness of a new experimental approach for assessing the antithrombotic potential of low molecular weight heparins (LMWH) such as dalteparin. In this approach, sera obtained from healthy volunteers treated with various i.v. doses of dalteparin (30, 60 or 120 anti-Xa IU/kg) or placebo (physiological saline) were used as the thrombogenic challenge in a Wessler's stasis model of experimental venous thrombosis in the rat. Sera from placebo-treated volunteers showed a stable thrombogenic activity (0.25 ml/kg of serum producing thrombi of about 50 mg wet weight). Sera from healthy volunteers having previously received dalteparin however demonstrated dose- and time-related reductions in their thrombogenic activity. Half-lives of these effects were 300. 444 and > 480 min for 30, 60 and 120 anti-Xa IU/kg dalteparin respectively. These values were significantly higher than the corresponding anti-Xa and anti-IIa half-lives.

Animals↗
PubMed1996

[Forensic medical implications of anticoagulant treatments].

Several types of accidents related to anticoagulant treatment can lead to legal procedures, including: thromboembolic post-operative complications associated with lack of anticoagulant prophylaxis and leading to sequelae or death; severe hemorrhagic or thromboembolic accidents attributed to poor management of anticoagulant therapy; complications with sequelae or death resulting from heparin-induced thrombopenia, either with standard or low-molecular weight heparin and associated with poor surveillance of platelet counts. The exceptional nature of accidents leading to legal procedures (24 legal cases in Pr Natali's experience) and the small number of other cases reported should not lead to underestimating the importance of precise rules for anticoagulation treatments. In 7 cases, there was no anticoagulant prophylaxis after surgery. Recent consensus conferences have proposed a definition of small, moderate or high risk of thrombosis as a function of patient status and surgical procedure. Expert working groups have defined the operated patients for which pharmacological anti-coagulation is necessary. In 19 other cases, management of the treatment protocol was insufficient leading to severe hemorrhage with sequelae, severe thromboembolism, or late diagnosis of heparin-induced thrombocytopenia because of insufficient surveillance of platelet counts. Recent advances in laboratory tests for the diagnosis of heparin-induced thrombocytopenia should be emphasized. To these case reports can be added other observations in a small number of complaints resulting from unadvisable treatment combinations, poor surveillance of a thromboembolic event or dangerous invasive exploration.

Adult↗
PubMed1995

[Platelet collection by apheresis with reduced use of citrate: quantitative and qualitative evaluation of three protocols].

Three protocols of platelet collection by apheresis on Cobe Spectra with different citrate concentrations were compared. First we determined until what level we could diminish the ratio anticoagulant/whole blood flow to enhance the efficiency without clotting in the cell separator by platelet aggregates. We found that protocol 2 had a better platelet collection efficiency than the standard protocol 1: respectively 59% versus 52%. Protocol 3 had even a better efficiency but, due to the risk of clotting (5% of the procedures) we rejected it for routine use. We compared in vitro platelet functions of protocols 1 and 2 by aggregometry in vitro. The results with the different aggregating agents indicated that the less citrated environment kept the platelets more functional in vitro. A disadvantage of protocol 2 compared to the standard protocol is the more important number of platelet concentrates that contain more than 10(6) leucocytes.

Adult↗
PubMed1995

Peripheral-T-cell lymphoma with hemophagocytic histiocytosis localised to the bone marrow associated with inappropriate secretion of antidiuretic hormone.

A patient with high fever, loss of weight and profound pancytopenia is reported. Peripheral T-cell lymphoma with hemophagocytosis was diagnosed. Bone marrow was the only localisation of the lymphoma. At presentation there were (i) a coagulopathy consistent with hemophagocytic histiocytosis (ii) the features of the syndrome of inappropriate antidiuretic hormone secretion (SIADH). These different abnormalities disappeared after chemotherapy and reappeared during each of the 2 periods of disease progression. The patient died 6 months after diagnosis without ever achieving complete remission. As far as we are aware this is the first case report of T-cell lymphoma with hemophagocytic syndrome localised to the bone marrow and associated with SIADH.

Aged↗
PubMed1995

[Value of the determination of D-dimers in the diagnostic approach of venous thrombo-embolic disorders].

The aim of this study is to evaluate the usefulness of plasma measurements of D-dimer using ELISA method and latex agglutination test in the diagnostic approach of venous thromboembolism. Among 126 patients suspected of pulmonary embolism (80 pat.) or deep venous thrombosis of the legs (46 pat.), the diagnosis of acute venous thromboembolism has been confirmed using gold standard invasive techniques (pulmonary angiography and/or contrast venography) in 49% of them. The sensitivity, specificity, negative predictive value and positive predictive value of a D-dimer plasma concentration above 500 ng/ml, on admission day, for the diagnosis of venous thromboembolism are 98%, 66%, 97%, 74% respectively when using the ELISA method, and 87%, 70%, 85%, 74% respectively when using the latex assay. In the 51 patients with a lung scan showing an indeterminate probability of pulmonary embolism, the sensitivity of the ELISA method is very high (94%) but that of the latex assay is low (67%). The repetition of D-dimer measurement on days 2 and 4 following admission has no significant effect on the sensitivity of the ELISA and latex assays. Our results demonstrate that the measurement of plasma D-dimer concentration using latex assay should not be used in the diagnostic approach of venous thromboembolism because the sensitivity of this test is insufficient for ruling out the presence of the disease. On the opposite, a low concentration of plasma D-dimer measured by the ELISA method might be used to rule out acute venous thromboembolism, and avoid invasive radiological techniques, especially in patients with an indeterminate probability lung scan.

Enzyme-Linked Immunosorbent Assay↗
PubMed1995

[Hypersensitivity and resistance to antivitamins K].

During the initial phase or during treatment with oral anticoagulants, hypersensitivity or resistance may be observed, requiring significant changes in prescribed dosage. A thorough knowledge of the mode of action of vitamin K and its antagonists is useful to improve understanding of unexpected response to oral anticoagulant therapy. These abnormal responses may be due to poor compliance to treatment by the patient, insufficient or excessive vitamin K intake, interference with other drugs or abnormalities of the hepatic enzymes which are the target of oral anticoagulant drugs. The search for a cause is justified by the risks associated with these abnormal responses. It must be rigorously undertaken with an accurate interrogation, use of an anticoagulation monitoring leaflet and, if necessary, measurement of plasma concentrations and pharmacokinetics of the anticoagulant drug.

4-Hydroxycoumarins↗
PubMed1995

Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC Subcommittee on Fibrinogen.

Approximately 250 cases of dysfibrinogenemia have been reported; 55% were asymptomatic (detected by chance), 25% had a tendency to bleeding, and 20% were reported to have a tendency to thrombosis. To establish a possible association between familial dysfibrinogenemia and thrombophilia, data on cases with both affections were collected in a study within the framework of the SSC Subcommittee on Fibrinogen of the International Society on Thrombosis and Haemostasis. Registry forms of 51 cases were received. Twenty-six cases fulfilled the (arbitrarily chosen) criteria of familial dysfibrinogenemia and of thrombosis not due to other causes. Protein C and protein S deficiency and APC resistance as a cause of thrombosis could not be excluded in probands on anticoagulants or investigated before the discovery of the assays. The prevalence of dysfibrinogenemia in patients with a history of venous thrombosis is low, i.e. 0.8%, as deduced from 9 studies in 7 countries on 2376 patients. The 26 cases fulfilling the criteria are characterized by predominantly venous thrombosis at a young age. Severe bleeding was rare and limited to bleeding post partum. Homozygosity was established in 2 cases (Marburg and Naples), hypodysfibrinogenemia (less than 1.5 mg antigen per ml) in 5 cases. A high incidence of problems related to pregnancy, in particular thrombosis post partum and spontaneous abortions was noted amongst the 15 women with thrombophilic dysfibrinogen. An association between dysfibrinogenemia and thrombophilia is indicated by studies on relatives of the 26 probands. Analysis of 187 investigated family members showed that thrombophilia affected 20 persons exclusively in the group of 99 relatives with dysfibrinogenemia, no thrombosis was reported in the group of 88 relatives without the defect. Convincing evidence for such an association became apparent for only 5 individual propositi of whom 2 or more family members had both the defect and thrombotic episodes at a young age (Caracas V, Frankfurt IV/Vlissingen, Melun, Naples and Paris V, also named Dusart). Mainly two mechanisms to explain thrombosis as a consequence of malfunctioning fibrinogen have been suggested: a) A defective binding of thrombin to abnormal fibrin which leads to increased thrombin levels (Malmö, Naples, New York I, Pamplona II, Poitiers), b) A defective stimulatory function of abnormal fibrin in the t-PA mediated fibrinolysis (Argenteuil, Chapel Hill III, Date, New York I, Nijmegen, Pamplona II, Paris V).(ABSTRACT TRUNCATED AT 400 WORDS)

Abortion, Spontaneous↗
PubMed1994

Laboratory monitoring of oral anticoagulant therapy.

The safety and success of oral anticoagulant treatment are dependent on laboratory control by the prothrombin time test. Until recently, the therapeutic range in prothrombin ratios of 2.0 to 2.5 resulted in greatly different dosage regimes, because of the lack of standardization of the test, particularly its thromboplastin component. Low-dose warfarin was associated with responsive thromboplastin. In North America and many other countries, a high-dose regime from high international sensitivity index thromboplastin caused more bleeding.

Administration, Oral↗
PubMed1994

French multicentric evaluation of recombinant tissue factor (recombiplastin) for determination of prothrombin time.

Recombiplastin, a recombinant a human tissue factor, elaborated by Ortho Diagnostic Systems, produced by Baculovirus and relipidated with highly purified phospholipids, was tested as a new reagent for determining prothrombin time (PT) in a French multicentric study. Its intralaboratory performances, including sensitivity, repeatability, reproducibility and stability, were explored to establish whether its use would reduce the interlaboratory dispersion of PT values, and therefore improve the standardization of oral anticoagulant treatment. The 9 university hospital hematology laboratories involved in this study used the same type of instrument (KC 10). For 10 consecutive days, they determined PTS on a normal plasma pool, plasma dilutions of 1/2, 1/3 and 1/8, 3 identical lyophilized calibrated plasmas, as well as plasmas from 20 normal subjects, 50 patients on oral anticoagulant therapy with Recombiplastin which has an International Sensitivity Index (ISI) of 1, and 2 commercial thromboplastin extracts (ISI #1 or 2). In the patients on anticoagulants, factors VII, X and V were measured when results were conflicting. The intra and interlaboratory reproducibilities of Recombiplastin, calculated on the basis of either PTS expressed in seconds, or of the International Normalized Ratio (INR), were good, with coefficients of variation (CV) similar to those observed with the 5 other reagents used by the different laboratories (2% < CV < 8%). The stability of Recombiplastin was excellent, with no variation in PT after 72 h of incubation at 37 degrees C. A normal PT of 12 s was obtained with Recombiplastin, similar to the values found for the reagents with ISI #2.(ABSTRACT TRUNCATED AT 250 WORDS)

Administration, Oral↗
PubMed1993

Problems of oral anticoagulation in an adult with homozygous protein C deficiency and late onset of thrombosis.

We describe a 57-year-old woman with homozygous protein C deficiency and mild thrombotic manifestations consisting of three spontaneous distal deep vein thromboses occurring after the age of 45. Previous surgery and pregnancies had been uneventful. Low but detectable protein C antigen and activity levels (both 20%) were discovered on the occasion of skin necrosis induced by oral anticoagulation. This therapy was interrupted because of skin necrosis and several episodes of disseminated intravascular coagulation (DIC) at the initiation of treatment despite a cautious protocol. No recurrent thromboembolic event has occurred in our patient using prophylactic doses of low molecular weight heparin for 24 months. New therapeutic approaches might be the administration of low molecular weight heparin or oral anticoagulation associated with protein C replacement in the induction period. This case reflects the variability of expression of protein C deficiency as well as the potential hazards of antivitamin K anticoagulation in this disorder.

Acenocoumarol↗
PubMed1993

Comparative effects of enoxaparin and unfractionated heparin in healthy volunteers on prothrombin consumption in whole blood during coagulation, and release of tissue factor pathway inhibitor.

In a randomized crossover study twelve healthy male volunteers (23.5 +/- of 4.8 years, 73.0 +/- 6.4 kg, 180.8 +/- 5.7 cm) received one subcutaneous injection of either enoxaparin (EN) at 40 mg or 1 mg kg-1, or unfractionated heparin (UH) at 5,000 IU at one week intervals. Area under curves (AUC) of Anti-Xa and Anti-IIa activities correlated with EN dose. The relative effectiveness of EN versus UH 5,000 U as assessed by AUC ratio (EN/UH) was 7 and 15 for Anti-Xa activity, 1.3 and 3.1 for Anti-IIa activity after sc injection of EN 40 mg (4,000 Anti-Xa IU and 1,200 Anti-IIa U) and 1 mg kg-1 (7,300 +/- 640 Anti-Xa IU and 2,190 +/- 290 Anti-IIa IU) respectively. In volunteers receiving EN, a dose dependent inhibition of thrombin generation rate in platelet depleted plasma (PDP), measured with a new and simple chromogenic thrombin generation assay, was observed when compared with baseline values. Similarly, intrinsic prothrombin activation in whole blood, evidenced by measuring residual factor II in serum 2 hours after clotting (prothrombin consumption test: PC), was inhibited in a dose dependent manner. In UH treated volunteers, although the inhibition of thrombin generation rate in PDP was similar to that observed with EN 40 mg, prothrombin consumption in whole blood was not significantly modified. Tissue factor pathway inhibitor (TFPI) activity release was increased similarly for UH and EN 40 (1.4 fold increase above baseline values) and 1.9 fold for the higher dose of EN. The discrepancy between prothrombin consumption in whole blood and inhibition of thrombin generation rate in PDP in the UH and not in the EN group strongly suggests that UH and not EN is influenced by the presence of a platelet component. This could be formed during thrombin induced platelet activation. Platelet factor 4 is a possible candidate. Another hypothesis involves the role of TFPI-UH complex anticoagulant activity which might be inhibited more during whole blood coagulation than the TFPI-EN complex.

Adult↗
PubMed1993

Small abnormal echos after mitral valve replacement with bileaflet mechanical prostheses: predisposing factors and effect on thromboembolism.

Early transesophageal echocardiography (TEE) after mitral valve replacement can detect symptomless, non-obstructive thrombus on prosthetic valves and also small filamentous abnormal echoes (SAE). The object of this study is to evaluate their respective frequency and predisposing factors. Between October 1988 and June 1992, 129 consecutive patients underwent mitral valve replacement with a bileaflet prosthesis and had transesophageal echocardiography at an average of 15 +/- 7 days (range: 6-35 days) after surgery. Details of postoperative anticoagulation were analyzed in 99 patients from five surgical centers having comparable postoperative anticoagulation protocols. Among those patients presenting with SAE, 76% had a second transesophageal echocardiography at an average of 145 +/- 166 days after the first examination. Mean age was 56 +/- 13 years. Small filamentous echoes were found in 55 patients (43%). In univariate analysis, independent predictors were age, absence of systolic regurgitation across the mitral prosthesis as observed with continuous Doppler, and the presence of spontaneous echo contrast (SC) in the left atrium: 54 +/- 14 years in the absence vs. 59 +/- 10 in the presence of SAE (p < 0.05); 54% of systolic leak vs. 36% (p < 0.05); 43% of SC vs. 75% (p < 0.00001). In multivariate analysis, spontaneous echo contrast was the only independent predictor for SAE (p < 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗